Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conceptualization of the gastrointestinal tract as the "motor" that drives sepsis and multiple-system organ failure has only recently been appreciated. Most of the investigation into the pathophysiology of gut-derived sepsis involves using animal models; however, some of the findings are already being corroborated in human studies. The gastrointestinal tract is a dynamic organ whose function as a front-line defense against infection needs to be appreciated. The development of lethal sepsis is a function of the microbial load and virulence, the status of the gastrointestinal barrier, and the magnitude of the host defense response. In assuming care of a critically ill patient, we must be judicious in the use of antibiotics in order to prevent intestinal overgrowth of potential pathogens. Providing proper nutrition by an enteral route (when possible) not only satisfies caloric needs but regulates the microflora and maintains the integrity of the mucosal barrier. Burn patients should receive enteral nutrition early, the first day if possible. This not only will protect the intestinal mucosa but also will blunt the hypermetabolic response following thermal injury. Lastly, the patient should not receive an excessive amount of narcotic or sedative, for these drugs have an inhibitory effect on gastrointestinal motility, encouraging bacterial overgrowth. In the near future, new therapeutic modalities may soon become available to protect and treat the compromised gastrointestinal barrier. These modalities may include, but certainly are not limited to, the use of glutamine and xanthine oxidase inhibitors to prevent stress-related injury to the gastrointestinal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
Plast Reconstr Surg 1992 Sep
PMID:The role of the gastrointestinal tract in the development of burn sepsis. 151 4

Benznidazole (Bz) (N-benzyl-2-nitro-1-imidazole acetamide) is a drug used against Chagas' disease, a parasitic disease afflicting several millions of Latin Americans. Bz administration to Sprague-Dawley male rats at 100 mg/kg p.o. caused subcellular alterations in the adrenal cortex involving fasciculata and reticularis zones but not in the glomerulosa. There is Bz nitroreductase activity in the adrenal microsomal and mitochondrial fractions but most of it is localized in mitochondria. Activity in the two fractions requires NADPH under anaerobic conditions. Mitochondrial Bz nitroreductase activity was inhibited by oxygen. A minor but statistically significant inhibition was observed in mixtures incubated under carbon monoxide. Microsomal Bz nitroreductase activity was not detected under oxygen atmosphere and was not inhibited under carbon monoxide. No Bz nitroreductase activity mediated by xanthine oxidase or aldehyde oxidase was detected in the cytosolic fraction from rat adrenals. Electron microscopic examination of the adrenal cortex from Bz-treated animals revealed cells with marked lipid accumulation and alterations in nuclei, endoplasmic reticulum and mitochondria in the reticularis and fasciculata zones. In vitro results suggest a Bz nitroreductive activation, with minor or null P-450 participation, leading to reactive metabolites able to cause damage in various organelles.
Toxicology 1992 Sep
PMID:Benznidazole-induced ultrastructural alterations in rat adrenal cortex. Mechanistic studies. 151 44

Treatment of rats with a single carcinogenic dose of CdCl2 (i.e., 30 mumol/kg) caused severe hemorrhagic damage in the testis within the first 12 h after the metal. Subsequently, atrophy with calcification developed in the next 2-3 mo. Atrophied tissues regenerated during the 1 yr after exposure. Twelve hours after exposure to the Cd treatment, lipid peroxidation levels, Fe content, and cellular production of H2O2 were remarkably elevated in testicular Leydig cells, the target cell population for Cd carcinogenesis. At the same time, glutathione peroxidase activity rose, glutathione reductase and catalase activities were reduced, and superoxide dismutase activity was unchanged. Xanthine oxidase activity in Leydig cells was also elevated at 6 and 9 h after the Cd treatment. Reduced glutathione in testes was decreased and oxidized glutathione was increased 12 h after exposure to the metal. These facts suggest that the carcinogenic doses of Cd induced oxidative stress while compromising cellular defense mechanisms against such stress. Therefore, active oxygen species such as H2O2 may have an important role in the initiation of carcinogenesis within the target cell population.
J Toxicol Environ Health 1992 Sep
PMID:Role of oxidative stress in single-dose, cadmium-induced testicular cancer. 152 11

Xanthine dehydrogenase (XDH) from the unicellular green alga Chlamydomonas reinhardtii has been purified to electrophoretic homogeneity by a procedure which includes several conventional steps (gel filtration, anion exchange chromatography and preparative gel electrophoresis). The purified protein exhibited a specific activity of 5.7 units/mg protein (turnover number = 1.9 .10(3) min-1) and a remarkable instability at room temperature. Spectral properties were identical to those reported for other xanthine-oxidizing enzymes with absorption maxima in the 420-450 nm region and a shoulder at 556 nm characteristic of molybdoflavoproteins containing iron-sulfur centers. Chlamydomonas XDH was irreversibly inactivated upon incubation of enzyme with its physiological electron donors xanthine and hypoxanthine, in the absence of NAD+, its physiological electron acceptor. As deduced from spectral changes in the 400-500 nm region, xanthine addition provoked enzyme reduction which was followed by inactivation. This irreversible inactivation also took place either under anaerobic conditions or whenever oxygen or any of its derivatives were excluded. Adenine, 8-azaxanthine and acetaldehyde which could act as reducing substrates of XDH were also able to inactivate it upon incubation. The same inactivating effect was observed with NADH and NADPH, electron donors for the diaphorase activity associated with xanthine dehydrogenase. In addition, partial activities of XDH were differently affected by xanthine incubation. We conclude that xanthine dehydrogenase inactivation by substrate is due to an irreversible process affecting mainly molybdenum center and that sequential and uninterrupted electron flow from xanthine to NAD+ is essential to maintain the enzyme in its active form.
Biochim Biophys Acta 1992 Sep 15
PMID:Purification and substrate inactivation of xanthine dehydrogenase from Chlamydomonas reinhardtii. 152 76

Neutrophils migrate to areas of inflammation and, when stimulated, produce O2-, H2O2, and other reactive O2 metabolites. To assess the effects of stimulated neutrophils on enterocytes, rat enterocytes were incubated with peripheral neutrophils. To assess cell viability, trypan blue exclusion and lactate dehydrogenase and protein release were measured. When 10(6) enterocytes/mL were incubated with 2.5 x 10(5) neutrophils/mL stimulated with phorbol myristate acetate, trypan blue exclusion decreased and lactate dehydrogenase and protein release increased. With the addition of 0.10 mg/mL of superoxide dismutase, trypan blue exclusion further decreased and lactate dehydrogenase and protein release increased. This suggests that H2O2- or H2O2/O2(-)-derived metabolites are more damaging to isolated enterocytes than O2-. To test this hypothesis, enterocytes were incubated with xanthine and increasing concentrations of xanthine oxidase in the presence and absence of superoxide dismutase. With increasing concentrations of xanthine oxidase, the cell number decreased and protein release increased. With the addition of superoxide dismutase, fewer cells were present, suggesting that cell lysis occurred. Protein release was further increased by the addition of superoxide dismutase. Enterocytes were then incubated with leucine and increasing concentrations of amino acid oxidase. With increasing concentrations of amino acid oxidase, trypan blue exclusion decreased and protein and lactate dehydrogenase release increased. These effects were ameliorated by the addition of 500 IU catalase/mL. These data suggest that O2- and H2O2, whether created by stimulated neutrophils or an enzyme-generating system, are damaging to isolated enterocytes. Superoxide dismutase did not offer enterocytes protection.
Gastroenterology 1991 Sep
PMID:Rat enterocyte injury by oxygen-dependent processes. 165 Mar 18

Metabolic redox cycling between the stilbene estrogen diethylstilbestrol (DES) and diethylstilbestrol-4',4"-quinone (DES Q) has been demonstrated previously. The xanthine and xanthine oxidase-catalyzed reduction of estrogen quinone has been studied in this work to understand the role of metabolic redox cycling in estrogen metabolism. Xanthine and xanthine oxidase catalyzed the reduction of DES Q to 44% Z-DES and 9% E-DES. This reaction was inhibited by the addition of superoxide dismutase or by a lack of oxygen (under anaerobic conditions). DES Q was also reduced in a non-enzymatic reaction by superoxide radicals generated by potassium superoxide and crown ether. The reaction between the O2-. and DES Q was also investigated by an electron spin resonance spin-trapping technique. The superoxide anion generated in an oxygen-saturated xanthine and xanthine oxidase system was detected as 5,5-dimethyl-1-pyrroline-1-oxide-superoxide adduct. The addition of DES Q or 2,3-estradiol quinone totally inhibited the formation of this adduct. The reduction of DES Q by superoxide radicals was taken as evidence that this reaction was one possible mechanism of xanthine and xanthine oxidase-mediated reduction. In addition, reduction of DES Q by direct electron transfer to quinone by the enzyme may also occur. The intermediate formation of semiquinone free radicals in the reduction is implied by the nature of the single electron transfer reactions and, in addition, has been demonstrated for the catechol estrogen by electron spin resonance measurements. It is concluded that the reduction of estrogen quinones to their hydroquinones by xanthine oxidase occurs by both one electron transfer to the quinone and by formation of superoxide which then reduces the quinone.
Biochem Pharmacol 1991 Sep 27
PMID:Xanthine oxidase-catalyzed reduction of estrogen quinones to semiquinones and hydroquinones. 165 92

Oxygen radical generation in the xanthine- and NADH-oxygen reductase reactions by xanthine oxidase, was demonstrated using the ESR spin trap 5,5'-dimethyl-1- pyrroline-N-oxide. No xanthine-dependent oxygen radical formation was observed when allopurinol-treated xanthine oxidase was used. The significant superoxide generation in the NADH-oxygen reductase reaction by the enzyme was increased by the addition of menadione and adriamycin. The NADH-menadione and -adriamycin reductase activities of xanthine oxidase were assessed in terms of NADH oxidation. From Lineweaver-Burk plots, the Km and Vmax of xanthine oxidase were estimated to be respectively 51 microM and 5.5 s-1 for menadione and 12 microM and 0.4 s-1 for adriamycin. Allopurinol-inactivated xanthine oxidase generates superoxide and OH.radicals in the presence of NADH and menadione or adriamycin to the same extent as the native enzyme. Adriamycin radicals were observed when the reactions were carried out under an atmosphere of argon. The effects of superoxide dismutase and catalase revealed that OH.radicals were mainly generated through the direct reaction of H2O2 with semiquinoid forms of menadione and adriamycin.
J Biochem 1991 Sep
PMID:Allopurinol-insensitive oxygen radical formation by milk xanthine oxidase systems. 166 14

A technique for the separation of neutrophils from macrophages-epithelial cells in samples of nonmastitic bovine milk with low cell counts has been developed. The procedure is based on centrifugation in a discontinuous metrizamide gradient and is rapid, taking less than 40 min. The recovery of the neutrophils is about 30% and their viability about 90%. The isolated neutrophils showed an appreciable unstimulated luminol- and lucigenin-dependent chemiluminescence, which was due to NADPH oxidase rather than to xanthine oxidase. The neutrophils had a higher rate of ingestion of C3-opsonized particles than macrophages-epithelial cells, whereas no significant differences in phagocytosis of IgG-opsonized yeast or unopsonized yeast were detected between the two cell populations. The macrophages-epithelial cells produced no luminol-dependent chemiluminescence and induced considerably lower activity in the lucigenin-dependent system than neutrophils, indicating that these cells contain no myeloperoxidase. Analyses of the activity of the neutrophils in response to C3-opsonized yeast particles showed that the luminol-dependent chemiluminescence of cells isolated from residual milk increased significantly over the lactation period. Moreover, a tendency to a higher phagocytosis and chemiluminescence of neutrophils isolated from residual milk than from stripping milk was indicated.
J Dairy Sci 1991 Sep
PMID:Isolation and phagocytic properties of neutrophils and other phagocytes from nonmastitic bovine milk. 172 16

The rates of NADH oxidation in presence of xanthine oxidase increase to a small and variable extent on addition of high concentrations of lactate dehydrogenase and other dehydrogenases. This heat stable activity is similar to polyvanadate-stimulation with respect to pH profile and SOD sensitivity. Isocitric dehydrogenase (NADP-specific) showed heat labile, SOD-sensitive polyvanadate-stimulated NADH oxidation activity. Polyvanadate-stimulated SOD-sensitive NADH oxidation was also found to occur with riboflavin, FMN and FAD in presence of a non-specific protein, BSA, suggesting that some flavoproteins may possess this activity.
Mol Cell Biochem 1991 Sep 18
PMID:Stimulation of NADH oxidation by xanthine oxidase and polyvanadate in presence of some dehydrogenases and flavin compounds. 178 72

In cytosolic fraction of adult Paragonimus westermani, superoxide dismutase activity was identified (4.3 units/mg of specific activity) using a xanthine-xanthine oxidase system. The enzyme was purified 150 fold in its activity using the ammonium sulfate precipitation, DEAE-Trisacryl M anion-exchange chromatography and Sephadex G-100 molecular sieve chromatography. The enzyme exhibited the enhanced activity at pH 10.0. The enzyme activity totally disappeared in 1.0mM cyanide while it remained 77.8% even in 10 mM azide. These findings indicated that the enzyme was Cu, Zn-SOD type. Molecular mass of the enzyme was estimated to be 34 kDa by gel filtration and 17 kDa on reducing SDS-polyacrylamide gel electrophoresis which indicated a dimer protein.
Kisaengchunghak Chapchi 1991 Sep
PMID:Purification and characterization of a Cu, Zn-superoxide dismutase from adult Paragonimus westermani. 178 52


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